Objective Hair greying (i.e., canities) is a component of chronological ageing and occurs regardless of gender or ethnicity. Canities is directly linked to the loss of melanin and increase in oxidative stress in the hair follicle and shaft. To promote hair pigmentation and reduce the hair greying process, an agonist of -melanocyte-stimulating hormone (-MSH), a biomimetic peptide (palmitoyl tetrapeptide-20; PTP20) was developed. The aim of this study was to describe the effects of the designed peptide on hair greying. MethodsResultsEffect of the PTP20 on the enzymatic activity of catalase and the production of H2O2 by Human Follicle Dermal Papilla Cells (HFDPC) was evaluated. Influence of PTP20 on the expression of melanocortin receptor-1 (MC1-R) and the production of melanin were investigated. Enzymatic activity of sirtuin 1 (SIRT1) after treatment with PTP20 was also determined. Ex vivo studies using human micro-dissected hairs allowed to visualize the effect of PTP20 on the expression in hair follicle of catalase, TRP-1, TRP-2, Melan-A, ASIP, and MC1-R. These investigations were completed by a clinical study on 15 human male volunteers suffering from premature canities. The in vitro and ex vivo studies revealed the capacity of the examined PTP20 peptide to enhance the expression of catalase and to decrease (30%) the intracellular level of H2O2. Moreover, PTP20 was shown to activate in vitro and ex vivo the melanogenesis process. In fact, an increase in the production of melanin was shown to be correlated with elevated expression of MC1-R, TRP-1, and Melan-A, and with the reduction in ASIP expression. A modulation on TRP-2 was also observed. The pivotal role of MC1-R was confirmed on protein expression analysed on volunteer's plucked hairs after 3 months of the daily application of lotion containing 10 ppm of PTP20 peptide. ConclusionResumeThe current findings demonstrate the ability of the biomimetic PTP20 peptide to preserve the function of follicular melanocytes. The present results suggest potential cosmetic application of this newly designed agonist of -MSH to promote hair pigmentation and thus, reduce the hair greying process. ObjectifMethodesLe blanchiment des cheveux (i.e., canitie) est un element du vieillissement chronologique qui se produit independamment du genre ou de l'ethnie. La canitie est directement liee a la perte de melanine et a l'augmentation du stress oxydatif dans le follicule et la tige pilaires. Pour favoriser la pigmentation des cheveux et reduire le processus de blanchiment des cheveux, un agoniste de l'<< -melanocyte-stimulating hormone >> (-MSH), un peptide biomimetique (<< palmitoyl tetrapeptide-20 >>; PTP20) a ete developpe. Le but de cette etude est de decrire les effets de ce peptide concu, sur le blanchiment des cheveux. L'effet du PTP20 a ete evalue sur l'activite enzymatique de la catalase et la production de H2O2 par les cellules humaines de la papille dermique du follicule pileux (<< Human Follicle Dermal Papilla Cells >>, HFDPC). L'influence du PTP20 sur l'expression du recepteur a la melanocortine (<< melanocortin receptor-1 >>, MC1-R) et sur la production de melanine ont ete etudies. L'activite enzymatique de la sirtuine 1 (SIRT1), apres traitement avec PTP20, a aussi ete determinee. Des etudes ex vivo sur cheveux humains microdisseques ont permis de visualiser l'effet du PTP20 sur l'expression de la catalase, TRP-1, TRP-2, Melan-A, ASIP et MC1-R, dans le follicule pileux. Ces etudes ont ete completees par un essai clinique incluant 15 volontaires masculins souffrant de canitie precoce. ResultatsConclusionLes etudes in vitro et ex vivo ont revele la capacite du peptide PTP20 examine, a augmenter l'expression de la catalase et a diminuer (30%) le niveau intracellulaire de H2O2. De plus, il a ete montre que PTP20 activait le processus de melanogenese in vitro et ex vivo. En fait, il a ete montre qu'une augmentation de la production de melanine etait correlee avec une expression plus elevee de MC1-R, TRP-1 et Melan-A, ainsi qu'avec une reduction de l'expression d'ASIP. Une modulation de TRP-2 a aussi ete observee. Le role cle de MC1-R a ete confirme apres analyse d'expressions proteiques, sur les cheveux epiles des volontaires, apres 3 mois d'application quotidienne d'une lotion contenant 10 ppm du peptide PTP20. Les conclusions actuelles demontrent la capacite du peptide biomimetique PTP20 a preserver la fonction des melanocytes folliculaires. Les resultats presentes suggerent une potentielle application cosmetique de cet agoniste d' -MSH nouvellement concu, pour favoriser la pigmentation et par consequent, reduire le processus de blanchiment des cheveux.

SynopsisThe naturally occurring tetrapeptide acetyl‐N‐Ser‐Asp‐Lys‐Pro (AcSDKP) recognized as a potent angiogenic factor was shown recently to contribute to the repair of cutaneous injuries. In the current article, we report the ability of AcSDKP to exert a beneficial effect on normal healthy skin and scalp and to compensate for the ageing process. In vitro AcSDKP at 10−11–10−7 M significantly stimulates the growth of human keratinocytes, fibroblasts and follicle dermal papilla cells. Moreover, it enhances the growth of human epidermal keratinocyte progenitor and stem cells as shown in a clonogenic survival assay. Topical treatment of ex vivo cultured skin explants with 10−5 M AcSDKP increases the thickness of the epidermis and upregulates the synthesis of keratins 14 and 19, fibronectin, collagen III and IV as well as the glycoaminoglycans (GAGs). In the ex vivo‐cultured hair follicles, AcSDKP promotes hair shaft elongation and induces morphological and molecular modifications matching the criteria of hair growth. Furthermore, AcSDKP at 10−11–10−7 M was shown to improve epidermal barrier, stimulating expression of three protein components of tight junctions (claudin‐1, occludin, ZO‐1) playing an important role in connecting neighbouring cells. This tetrapeptide exercises also activation of SIRT1 implicated in the control of cell longevity. Indeed, a two‐fold increase in the synthesis of SIRT1 by cultured keratinocytes was observed in the presence of 10−11–10−7 M AcSDKP. In conclusion, these findings provide convincing evidence of the regulatory role of AcSDKP in skin and hair physiology and suggest a cosmetic use of this natural tetrapeptide to prevent skin ageing and hair loss and to promote the cutaneous regeneration and hair growth.